Investigating Tumor Growth Dynamics Using Multimodal Contrast Agents and Optical

描述(由申请人提供)：本申请涉及广泛的挑战领域(06)使能技术和具体的挑战主题，06-CA-116：物理科学和细胞力学。我们将开发具有互补纳米颗粒探针的分析成像能力，以非侵入性方式测量细胞和组织的粘弹性属性。这些能力将被应用于了解肿瘤生长动力学的生物力学因素。具有磁核的近红外(NIR)吸收金纳米粒子将作为多光子成像的多模式造影剂，并用于磁动力光学相干层析成像(MM-OCT)和弹性成像(MM-OCE)，以表征肿瘤细胞和组织随着其发展而发生的粘弹性变化。将肿瘤细胞负载纳米探针，与成纤维细胞或巨噬细胞共培养，进行MM-OCE体外多模式成像。移植的肿瘤也将从携带纳米探针的肿瘤细胞中培养出来，然后切除进行体外成像，结果与传统的肿瘤发展指标(即视觉检查和组织学)相对照。我们预计这种方法可以揭示浸润性癌发展过程中关键的生物力学差异，在侵袭性癌中，细胞经历了从高抗张强度的肿胀状态到与迁移和渗出相关的可塑性和变形状态的转变。我们的具体目标如下： 1)光学相干层析成像(OCT)集成光学平台的构建 弹性成像(OCE)，用于具有细胞分辨率的肿瘤组织的非侵入性成像； 2)制造将等离子激元共振与磁动活动相结合的纳米探针，以 生成用于3D成像和弹性成像的独特近红外签名； 3)多通道同时成像平台的优化部署 装载纳米探针的肿瘤细胞和切除的肿瘤组织的成像和粘弹性分析。

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (06) Enabling Technologies and specific Challenge Topic, 06-CA-116: Physical Sciences and Cellular Mechanics. We will develop analytical imaging capabilities with complementary nanoparticle probes to measure the viscoelastic properties of cells and tissues in a noninvasive manner. These capabilities will be applied toward understanding biomechanical factors on tumor growth dynamics. Near-infrared (NIR) absorbing Au nanoparticles with magnetic cores will serve as multimodal contrast agents for multiphoton imaging and for magnetomotive optical coherence tomography (MM-OCT) and elastography (MM-OCE), to characterize viscoelastic changes in tumor cells and tissues as a function of their development. Tumor cells will be laden with nanoprobes and cocultured with fibroblasts or macrophages for in vitro multimodal imaging with MM-OCE. Tumor xenografts will also be grown in mice from nanoprobe-laden tumor cells, then excised for ex vivo imaging with results collated with conventional metrics of tumor development (i.e., visual inspection and histology). We anticipate this approach can reveal critical biomechanical differences in the development of invasive carcinomas, in which cells undergo transformations from turgid states with high tensile strength to plastic and deformable states associated with migration and extravasation. Our Specific Aims are as follows: 1) Construction of an integrated optical platform for optical coherence tomography (OCT) and elastography (OCE), for noninvasive imaging of tumor tissues with cellular resolution; 2) Fabrication of nanoprobes that combine plasmon resonance with magnetomotive activity, to generate unique NIR signatures for 3D imaging and elastography; 3) Optimization and deployment of the multimodal imaging platform for simultaneous structural imaging and viscoelastic profiling of nanoprobe-laden tumor cells and excised tumor tissues.